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Sensors (Basel, Switzerland) Jan 2022Nowadays, radon gas exposure is considered one of the main health concerns for the population because, by carrying about half the total dose due to environmental...
Nowadays, radon gas exposure is considered one of the main health concerns for the population because, by carrying about half the total dose due to environmental radioactivity, it is the second cause of lung cancer after smoking. Due to a relatively long half-life of 3.82 days, the chemical inertia and since its parent Ra-226 is largely diffuse on the earth's crust and especially in the building materials, radon can diffuse and potentially saturate human habitats, with a concentration that can suddenly change during the 24 h day depending on temperature, pressure, and relative humidity. For such reasons, 'real-time' measurements performed by an active detector, possibly of small dimensions and a handy configuration, can play an important role in evaluating the risk and taking the appropriate countermeasures to mitigate it. In this work, a novel algorithm for pattern recognition was developed to exploit the potentialities of silicon active detectors with a pixel matrix structure to measure radon through the emission, in a simple measurement configuration, where the device is placed directly in air with no holder, no collection filter or electrostatic field to drift the radon progenies towards the detector active area. This particular measurement configuration (dubbed as ) requires an /-discrimination method that is not based on spectroscopic analysis: as the gas surrounds the detector the particles are emitted at different distances from it, so they lose variable energy amount in air depending on the traveled path-length which implies a variable deposited energy in the active area. The pixels matrix structure allows overcoming this issue because the interaction of , and particles generate in the active area of the detector (group of pixels where a signal is read) of different shape and energy dispersion. The novel algorithm that exploits such a phenomenon was developed using a pixelated silicon detector of the TimePix family with a compact design. An (Am-241) and a (Sr-90) source were used to calibrate the algorithm and to evaluate its performances in terms of rejection capability and recognition efficiency. Successively, the detector was exposed to different radon concentrations at the ENEA-INMRI radon facility in 'bare' configuration, in order to check the linearity of the device response over a radon concentration range. The results for this technique are presented and discussed, highlighting the potential applications especially the possibility to exploit small and handy detectors to perform radon active measurements in the simplest configuration.
Topics: Air Pollutants, Radioactive; Algorithms; Humans; Radiation Monitoring; Radon; Radon Daughters
PubMed: 35062477
DOI: 10.3390/s22020516 -
Oncology Reviews 2022Due to their electrostatic nature, radon decay products can attach to solid particles and aerosols in the air. Inhalation and ingestion are therefore the two main routes... (Review)
Review
Due to their electrostatic nature, radon decay products can attach to solid particles and aerosols in the air. Inhalation and ingestion are therefore the two main routes through which people are exposed to radon and its decay products. During the inhalation of these radioactive aerosols, deposition takes place in different regions of the human respiratory tract. The deposited aerosols carrying radon and its progeny undergo a continuous radioactive transformation and expose the lung to ionizing alpha radiation, which can destroy the sensitive cells in the lung, causing a mutation that turns cancerous. Radon which is a colorless, odorless, and tasteless radioactive noble gas is a major health concern and is the second leading cause of lung cancer. To address this, an indoor radon survey was conducted in many countries internationally, with results showing that indoor radon concentration has a seasonal variation. This is due to the fluctuation of environmental parameters and the geological nature of buildings. Its concentration was found to be maximum in the cool (winter) season and a minimum concentration was recorded in the warm (summer) season of the year.
PubMed: 36531161
DOI: 10.3389/or.2022.10570 -
Journal of Nuclear Medicine : Official... Oct 2022Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety...
Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety of clinical trials for primary and metastatic cancers to bone. Clinical evaluation of Ra hematologic safety showed a significantly increased rate of neutropenia and thrombocytopenia in patients, hinting at myelosuppression as a side effect. In this study, we investigated the consequences of Ra treatment on bone marrow biology by combining flow cytometry, single-cell RNA sequencing, three-dimensional multiphoton microscopy and bone marrow transplantation analyses. Ra accumulated in bones and induced zonal radiation damage confined to the bone interface, followed by replacement of the impaired areas with adipocyte infiltration, as monitored by 3-dimensional multiphoton microscopy ex vivo. Flow cytometry and single-cell transcriptomic analyses on bone marrow hematopoietic populations revealed transient, nonspecific Ra-mediated cytotoxicity on resident populations, including stem, progenitor, and mature leukocytes. This toxicity was paralleled by a significant decrease in white blood cells and platelets in peripheral blood-an effect that was overcome within 40 d after treatment. Ra exposure did not impair full hematopoietic reconstitution, suggesting that bone marrow function is not permanently hampered. Our results provide a comprehensive explanation of Ra reversible effects on bone marrow cells and exclude long-term myelotoxicity, supporting safety for patients.
Topics: Alpha Particles; Bone Marrow; Bone and Bones; Flow Cytometry; Humans; Male; Radioisotopes
PubMed: 35177425
DOI: 10.2967/jnumed.121.263310 -
Molecules (Basel, Switzerland) Apr 2021Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after... (Review)
Review
Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after cancer cells have colonized the bone and co-opted the normal bone remodeling process. In addition to bone-targeted therapies (e.g., bisphosphonate and denosumab), hormone therapy, chemotherapy, external beam radiation therapy, and surgical intervention, attempts have been made to use systemic radiotherapy as a means of delivering cytocidal radiation to every bone metastatic lesion. Initially, several bone-seeking beta-minus-particle-emitting radiopharmaceuticals were incorporated into the treatment for bone metastases, but they failed to extend the overall survival in patients. However, recent clinical trials indicate that radium-223 dichloride (RaCl), an alpha-particle-emitting radiopharmaceutical, improves the overall survival of prostate cancer patients with bone metastases. This success has renewed interest in targeted alpha-particle therapy development for visceral and bone metastasis. This review will discuss (i) the biology of bone metastasis, especially focusing on the vicious cycle of bone metastasis, (ii) how bone remodeling has been exploited to administer systemic radiotherapies, and (iii) targeted radiotherapy development and progress in the development of targeted alpha-particle therapy for the treatment of prostate cancer bone metastasis.
Topics: Alpha Particles; Bone Neoplasms; Humans; Ligands; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiopharmaceuticals
PubMed: 33918705
DOI: 10.3390/molecules26082162 -
European Journal of Nuclear Medicine... Jun 2023
Topics: Humans; Male; Antigens, Surface; Astatine; Neoplasm Recurrence, Local; Precision Medicine; Prostatic Neoplasms
PubMed: 36862207
DOI: 10.1007/s00259-023-06178-4 -
Molecules (Basel, Switzerland) Nov 2019Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal... (Review)
Review
Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the α-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to date.
Topics: Alpha Particles; Animals; Antibodies, Monoclonal; Humans; Neoplasms; Radioisotopes; Radiometry; Radiopharmaceuticals
PubMed: 31779154
DOI: 10.3390/molecules24234314 -
Bioconjugate Chemistry Jul 2021Herein, we present the syntheses and characterization of a new undecadendate chelator, Hpy4pa, and its bifunctional analog Hpy4pa-phenyl-NCS, conjugated to the...
Herein, we present the syntheses and characterization of a new undecadendate chelator, Hpy4pa, and its bifunctional analog Hpy4pa-phenyl-NCS, conjugated to the monoclonal antibody, Trastuzumab, which targets the HER2+ cancer. Hpy4pa possesses excellent affinity for Ac (α, = 9.92 d) for targeted alpha therapy (TAT), where quantitative radiolabeling yield was achieved at ambient temperature, pH = 7, in 30 min at 10 M chelator concentration, leading to a complex highly stable in mouse serum for at least 9 d. To investigate the chelation of Hpy4pa with large metal ions, lanthanum (La), which is the largest nonradioactive metal of the lanthanide series, was adopted as a surrogate for Ac to enable a series of nonradioactive chemical studies. In line with the H NMR spectrum, the DFT (density functional theory)-calculated structure of the [La(py4pa)] anion possessed a high degree of symmetry, and the La ion was secured by two distinct pairs of picolinate arms. Furthermore, the [La(py4pa)] complex also demonstrated a superb thermodynamic stability (log ∼ 20.33, pLa = 21.0) compared to those of DOTA (log ∼ 24.25, pLa = 19.2) or Hmacropa (log = 14.99, pLa ∼ 8.5). Moreover, the functional versatility offered by the bifunctional py4pa precursor permits facile incorporation of various linkers for bioconjugation through direct nucleophilic substitution. In this work, a short phenyl-NCS linker was incorporated to tether Hpy4pa to Trastuzumab. Radiolabeling studies, serum stability, and animal studies were performed in parallel with the DOTA-benzyl-Trastuzumab. Both displayed excellent stability and tumor specificity.
Topics: Actinium; Alpha Particles; Animals; Antineoplastic Agents, Immunological; Chelating Agents; Coordination Complexes; Density Functional Theory; Humans; Mice; Radiopharmaceuticals; Thermodynamics; Tissue Distribution; Trastuzumab; Xenograft Model Antitumor Assays
PubMed: 32216377
DOI: 10.1021/acs.bioconjchem.0c00171 -
Journal of Medical Imaging and... Dec 2019This talk briefly reviews the earlier work in the field and highlights the contributions of colleagues whose clear vision paved the road for success of TAT. The talk... (Review)
Review
This talk briefly reviews the earlier work in the field and highlights the contributions of colleagues whose clear vision paved the road for success of TAT. The talk primarily will focus on the development of the radioisotopes for application in TAT. The challenges regarding release of daughter radioisotopes will be briefly discussed, and a summary of the alternative approaches for production of Ac will be presented.
Topics: Actinium; Alpha Particles; Humans; Neoplasms; Radioisotopes; Radiotherapy
PubMed: 31420270
DOI: 10.1016/j.jmir.2019.07.002 -
Life (Basel, Switzerland) Mar 2023Space missions with humans expose the crews to ionizing radiation, mainly due to the galactic cosmic radiation (GCR). All radiation protection programs in space aim to...
Space missions with humans expose the crews to ionizing radiation, mainly due to the galactic cosmic radiation (GCR). All radiation protection programs in space aim to minimize crews' exposure to radiation. The radiation protection of astronauts can be achieved through the use of shields. The shields could serve as a suit to reduce GCR exposure and, in an emergency, as a radiation shelter to perform necessary interventions outside the space habitat in case of a solar proton event (SPE). A space radiation shielding that is suitable for exploration during space missions requires particular features and a proper knowledge of the radiation type. This study shows the results of numerical simulations performed with the Geant4 toolkit-based code DOSE. Calculations to evaluate the performance of Nomex, an aramidic fiber with high mechanical resistance, in terms of dose reduction to crews, were performed considering the interaction between protons with an energy spectrum ranging from 50 to 1100 MeV and a target slab of 20 g/cm. This paper shows the properties of secondary products obtained as a result of the interaction between space radiation and a Nomex target and the properties of the secondary particles that come out the shield. The results of this study show that Nomex can be considered a good shield candidate material in terms of dose reductions. We also note that the secondary particles that provide the greatest contribution to the dose are protons, neutrons and, in a very small percentage, α-particles and Li ions.
PubMed: 36983945
DOI: 10.3390/life13030790 -
Cancer Research Nov 2019Alpha-emitter radiopharmaceutical therapy (α-RPT) is a treatment modality that is impervious to conventional cellular resistance mechanisms because of the unique...
Alpha-emitter radiopharmaceutical therapy (α-RPT) is a treatment modality that is impervious to conventional cellular resistance mechanisms because of the unique properties of the α-particle. Radiobiological studies of α-particle emitters have been few as they require detailed consideration of both biology and physics. Clinical studies of this radiation delivery modality have shown highly promising results in cancers that are resistant to other treatments. The work by Yard and colleagues published in this issue introduces an innovative approach to radiobiological investigations of α-RPT and highlights the specific physics considerations required to properly investigate this multidisciplinary treatment modality..
Topics: Alpha Particles; Humans; Neoplasms; Radiobiology; Radiopharmaceuticals
PubMed: 31676677
DOI: 10.1158/0008-5472.CAN-19-2806